Freedom from locoregional relapse at 2 years was 88-89% with or without chemotherapy. Patients randomized to CRT had a small numerical advantage in freedom from relapse at 5 years, 87% versus 83%. Neither disease-free (DFS) nor overall survival (OS) differed significantly between treatment groups at 2 or 5 years, according to Sandro Virgilio Porceddu, MD, of Princess Alexandra Hospital in Brisbane, Australia, and colleagues.

The addition of platinum-based chemotherapy did increase treatment-related toxicity, they reported online in the Journal of Clinical Oncology.

"Given the high locoregional control (LRC), interventions that may affect both LRC and distant metastases would be preferable for future adjuvant trials," the authors concluded. "Promising results with immune checkpoint inhibitors in advanced cutaneous squamous cell carcinoma of the head and neck (cSCCHN) warrant further evaluation in the adjuvant setting."

Two U.S. specialists in head and neck RT said the results should have a practice-changing impact on management of cSCCHN.

"While many physicians extrapolated from data demonstrating benefit to postoperative concurrent chemoradiation for high-risk mucosal squamous carcinomas, and integrated the same practice to high-risk cutaneous squamous carcinomas, these data suggest there is no benefit," Beth Beadle, MD, of Stanford University in Stanford, California and Thomas Galloway, MD, of Fox Chase Cancer Center in Philadelphia said in an email. "Of note, there is an exceptionally high 2-year freedom from locoregional recurrence of 88% for high-risk patients managed with surgery plus RT alone, which may serve as a benchmark for future studies; overall, these patients are doing well."

"Although some will criticize the use of carboplatin (compared to cisplatin) as the concurrent agent, fundamentally these results support the use of adjuvant radiation alone in patients with resected high-risk cutaneous malignancies," added Beadle and Galloway, clinical experts for the American Society for Radiation Oncology (ASTRO).

In contrast, the authors of an accompanying editorial concluded that the trial left unresolved the question of whether chemotherapy -- or other therapy -- has a role in high-risk cSCCHN. High-level evidence for cisplatin is still lacking, and relatively few patients in both arms of the trial did not have key high-risk features, such as extracapsular extension (50%-55%) and positive margins (<10%). Moreover, perineural invasion and degree of differentiation were not part of the inclusion criteria.

"The low proportion of high-risk patients likely accounts for the low event rate observed in this study, contributing to the inadequate power of the study to answer the primary study question," wrote Roy H. Decker, MD, of Yale Cancer Center in New Haven, Connecticut, and colleagues.

Targeted therapies and immune checkpoint inhibitors have yet to be examined as potential risk-reducing treatment in the adjuvant setting, they added.

The comparison of CRT and RT in cSCCHN followed simultaneous publication of two randomized trials in the New England Journal of Medicine, showing improved disease control, progression-free survival, and OS with CRT in patients with high-risk mucosal SCCHN. Though many clinicians extrapolated the findings to high-risk cSCCHN, no high-level evidence supported the practice, Porceddu's group noted.

Investigators randomized 321 patients; 310 of received assigned treatment. After a median follow-up of 60 months, the 2-year rate of freedom from locoregional relapse was 88% for RT and 89% for CT. The 5-year rates were 83% and 87%, representing a 16% reduction in the hazard ratio, which did not achieve statistical significance (95% CI 0.46 to 1.55, P=0.58).

Chemotherapy-related adverse events included nausea (55%), thrombocytopenia (18%), anemia (16%), vomiting (15%), and infection (11%). Grade 3/4 adverse events were infrequent, occurring in no more than 1%-2% of patients in the chemotherapy arm.

The study was supported by the National Health and Medical Research Council -- Australian Government, Cancer Council Queensland, and Queensland government.

Porceddu disclosed relevant relationships with Merck, UpToDate, and Oral Oncology. One co-author was supported by the Australian government through Cancer Australia. Co-authors disclosed multiple relevant relationships with industry.

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